HDAC8 Inhibitor

HDAC6-IN-10 is a highly selective HDAC6 inhibitor with the IC₅₀ of 0.73 nM. HDAC6-IN-10 has 144~10941-fold selectivity over other HDAC isoforms. HDAC6-IN-10 shows anti-proliferative activities against multiple myeloma cells.

HDAC-IN-35 (Compound 14) is a potent, selective HDAC and VEGFR-2 inhibitor, with IC₅₀ values of 0.166 and 13.2 µM for HDAC6 and VEGFR-2, respectively.

PDE5/HDAC-IN-1 (Compound 26) is a potent phosphodiesterase 5 (PDE5) and HDAC inhibitor with IC₅₀ values of 46.3 nM and 14.5 nM, respectively. PDE5/HDAC-IN-1 induces cell apoptosis and shows anticancer activities.

HDAC6-IN-73 is a highly potent and selective HDAC6 inhibitor with an IC₅₀ of 0.007 μM ± 0.001, ~1771-fold selectivity over HDAC1, ~131-fold selectivity over HDAC8, and antiproliferative activity in hematological cancer cell lines.HDAC6-IN-73 can be used for the research of hematological malignancies.

HDAC-IN-38 (compound 13) is a potent HDAC inhibitor. HDAC-IN-38 shows similar micro-molar inhibitory activity toward HDAC1, 2, 3, 5, 6, and 8. HDAC-IN-38 increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy. HDAC-IN-38 also increases the level of histone acetylation (H3K14 or H4K5).

HDAC-IN-43 is a potent HDAC 1/3/6 inhibitor with IC₅₀ values of 82, 45, and 24 nM, respectively. HDAC-IN-43 is a weak PI3K/mTOR inhibitors with IC₅₀ values of 3.6 and 3.7 μM, respectively. HDAC-IN-43 shows broad anti-proliferative activity .

HDAC6-IN-27 (compound 8C) is a HDAC inhibitor with IC₅₀ vales of 15.9 nM 136.5 nM and 6180.2 nM for HDAC6, HDAC8 and HDAC1, respectively. HDAC6-IN-27 shows potent antiparasitic effects.

MC2590 is a potent pyridine-containing histone deacetylase (HDAC) inhibitor. MC2590 is a inhibitor of HDAC1-3, -6, -8, and -10 (class I/IIb-selective inhibitor) with IC₅₀s of 0.015 μM-0.156 μM. MC2590 also inhibits HDAC isoforms HDAC4, HDAC5, HDAC7, HDAC9, HDAC11 with IC₅₀s of 1.35 μM-3.98 μM. MC2625 induces G2/M cell cycle arrest and modulates pro- and anti-apoptotic microRNAs towards apoptosis induction.

HDAC-IN-94 is a potent, selective HDAC6 inhibitor (IC₅₀ = 4.5 nM). HDAC-IN-94 shows >1000-fold selectivity over HDAC8 and shows minimal activity against other isoforms (HDAC1-3/10). HDAC-IN-94 induces α-tubulin hyperacetylation, apoptosis, and G2/M cell cycle arrest, exhibiting potent anti-tumor efficacy with low cytotoxicity. HDAC-IN-94 can be used for neuroblastoma and glioblastoma research.

CDK/HDAC-IN-2 is a potent HDAC/CDK dual inhibitor with IC₅₀ of 6.4, 0.25, 45, >1000, 8.63, 0.30, >1000 nM for HDAC1, HDAC2, HDAC3, HDAC6,8, CDK1, CDK2, CDK4,6,7, respectively. CDK/HDAC-IN-2 shows excellent antiproliferative activities. CDK/HDAC-IN-2 induces apoptosis and cell cycle arrest at G2/M phase. CDK/HDAC-IN-2 shows potent antitumor efficacy.

HDAC6 ligand-7 (Compound 16a) is a positron emission tomography (PET) tracer for the deacetylase 6 (HDAC6) enzyme with a K_d value of 1.66 nM. HDAC6 ligand-7 exhibits excellent HDAC6 inhibitory activity, with IC₅₀ values of 2.7 and 3.7 nM for hHDAC6 and mHDAC6, respectively, and has high selectivity for HDAC1/4/7/8. HDAC6 ligand-7 after being radioactively labeled with fluorine-18, [¹⁸F]HDAC6 ligand-7 shows varying degrees of radioactive uptake in PET, which can reflect the specific binding to HDAC6. HDAC6 ligand-7 can be used for the study of HDAC6 imaging.

HDAC6-IN-11 (Compound 9) is a selective HDAC6 inhibitor with the IC₅₀ value of 20.7 nM. HDAC6-IN-11 has more than 300-fold selectivity over HDAC other isoforms. HDAC6-IN-11 shows anti-proliferative activities against cancer cells.

HDAC8-IN-4 is a selective inhibitor of HDAC8. HDAC8-IN-4 inhibits HDAC8 and HDAC3 with IC₅₀s of 0.15 and 12 μM.

C1A is a class I/II HDACs and sirtuin inhibitor with an IC₅₀ of 479 nM for HDAC6. C1A induces sustained acetylation of HDAC6 substrates, α-tubulin and HSP90. C1A shows srtong anticancer effcts, and induces apoptosis in cancer cells.

ALK/HDAC-IN-1 is a dual inhibitor for ALK and HDAC6, with IC₅₀s of 16 nM and 1.03 μM, respectively. ALK/HDAC-IN-1 exhibits antitumor activity.

HDAC-IN-9 is a potent and selective tubulin and HDAC dual inhibitor. HDAC-IN-9 inhibits the invasion and migration of A549 cells. HDAC-IN-9 shows potent antitumor and antiangiogenic effect in vitro and in vivo.

Top/HDAC-IN-2 (45b), a Top and HDAC dual inhibitor, exhibits potent antitumor activities and induces apoptosis.

HDAC8/BRPF1-IN-1 (Compound 23a) is a dual inhibitor of HDAC8 and BRPF1 with an IC₅₀ of 443 nM against human HDAC8 and a K_d of 67 nM against human BRPF1. HDAC8/BRPF1-IN-1 shows low in vitro activity against HDAC1 and 6.

HDAC/Top-IN-1 is an orally active and pan HDAC/Top dual inhibitor with IC₅₀s of 0.036 μM, 0.14 μM, 0.059 μM, 0.089 μM and 9.8 μM for HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8. HDAC/Top-IN-1 efficiently induces apoptosis with S cell-cycle arrest in HEL cells. HDAC/Top-IN-1 has exhibits excellent in vivo antitumor efficacy.

FLT3/HDAC-IN-3 is a dual inhibitor of FLT3 and HDAC. FLT3/HDAC-IN-3 potently inhibits FLT3 (IC₅₀ = 14 nM), HDAC1 (IC₅₀ = 27 nM), HDAC6 (IC₅₀ = 20 nM), and FLT3^D853Y (IC₅₀ = 55 nM), exhibits weak activity against HDAC8, and shows no activity against HDAC4. FLT3/HDAC-IN-3 possesses kinase selectivity, plasma stability, and stability in human liver microsomes. FLT3/HDAC-IN-3 demonstrates anti-proliferative effects in a variety of hematological malignancy cell lines. FLT3/HDAC-IN-3 shows efficacy in the Jeko-1 xenograft model without observed significant toxicity. FLT3/HDAC-IN-3 can be used in the study of hematological malignancies.